Dataset Information

Changes in fecal metabolic and lipidomic features by anti-TNF treatment and prediction of clinical remission in patients with ulcerative colitis.

ABSTRACT:

Background

Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported.

Objective

Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment.

Design

Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients (n = 116).

Methods

Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model.

Results

Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers.

Conclusion

Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment.

SUBMITTER: Kim SY

PROVIDER: S-EPMC10161336 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Changes in fecal metabolic and lipidomic features by anti-TNF treatment and prediction of clinical remission in patients with ulcerative colitis.

Kim Seok-Young SY Shin Seung Yong SY Park Soo Jung SJ Im Jong Pil JP Kim Hyo Jong HJ Lee Kang-Moon KM Kim Ji Won JW Jung Sung-Ae SA Lee Jun J Kang Sang-Bum SB Shin Sung Jae SJ Kim Eun Sun ES Kim You Sun YS Kim Tae Oh TO Kim Hyun-Soo HS Park Dong Il DI Kim Hyung Kil HK Kim Eun Soo ES Kim Young-Ho YH Teng Dennis D Kim Jong-Hwa JH Kim Wonyong W Saeed Maham M Moon Jung Min JM Kim Kisung K Choi Chang Hwan CH Choi Hyung-Kyoon HK

Therapeutic advances in gastroenterology 20230502

<h4>Background</h4>Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported.<h4>Objective</h4>Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment.<h4>Design</h4>Prospective, observational, multicenter study was conducted on moderate-to-severe ...[more]

PMID: 37153496

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Project description:BackgroundThe long-term outcomes of Ulcerative colitis (UC) after discontinuation of biological therapy are largely unknown. There is also a lack of accurate and validated markers that can predict outcome after withdrawal accurately. The aims of this study were to describe the long-term outcomes in UC patients following cessation of anti-TNF therapy and explore potential biomarkers as an approach towards precision medicine.MethodsSeventy-five patients with moderate to severe UC treated to remission with anti-tumor necrosis factor (TNF) were included in the study. This is a follow-up of previously reported UC outcomes. The patients were categorized as either "Remission" or "Relapse". The "Relapse" group was divided into subgroups determined by the highest treatment level needed to obtain remission the last 3 years of observation: non-biological therapy, biological therapy or colectomy. Remission were divided in long term remission (LTR), those using immunomodulating drugs (LTR + imids) and those using only 5-amino-salicylate (5-ASA) treatment (LTR) for the past 3 years. Analyses of mucosal gene expression by real-time PCR were performed.ResultsThe median (IQR) observation time of all patients included was 121 (111-137) months. Of the 75 patients, 46 (61%) did not receive biological therapy, including 23 (31%) in LTR ± imids. Of these 23 patients, 16 (21%) were defined as LTR with a median observation time of (IQR) 95 (77-113) months. In total 14 patients (19%) underwent colectomy during the 10 years after first remission. Mucosal TNF copies/µg mRNA < 10 000 at anti-TNF discontinuation predicted long-term remission, biological free remission and lower risk of colectomy with a HR 0.36 (0.14-0.92) for long-term remission, HR 0.17 (0.04-0.78) for biological free remission and HR 0.12 (0.01-0.91) for colectomy. IL1RL1 was normalized in LTR phenotype and higher in relapsing UC.ConclusionIn this 10-year follow-up of UC of patients with moderate to severe disease, 61% of patients experience an altered phenotype to a milder disease course without need of biological therapy. Twenty-one percent of the patients were LTR without any medication except of 5-ASA. Mucosal TNF gene expression and IL1RL1- transcripts may be of clinical utility for long term prognosis in development of precision medicine in UC.

Dataset Information

Changes in fecal metabolic and lipidomic features by anti-TNF treatment and prediction of clinical remission in patients with ulcerative colitis.

Background

Objective

Design

Methods

Results

Conclusion

Publications

Changes in fecal metabolic and lipidomic features by anti-TNF treatment and prediction of clinical remission in patients with ulcerative colitis.

Similar Datasets

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